OSPEMIFENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H23ClO2
Molecular Weight	378.891
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OCCOC1=CC=C(C=C1)C(=C(\CCCl)C2=CC=CC=C2)\C3=CC=CC=C3

InChI

InChIKey=LUMKNAVTFCDUIE-VHXPQNKSSA-N

InChI=1S/C24H23ClO2/c25-16-15-23(19-7-3-1-4-8-19)24(20-9-5-2-6-10-20)21-11-13-22(14-12-21)27-18-17-26/h1-14,26H,15-18H2/b24-23-

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203505s005lbl.pdf

Ospemifene (commercial name Osphena produced by Shionogi) is anoral medication indicated for the treatment of dyspareunia – pain during sexual intercourse – encountered by some women, more often in those who are post-menopausal. Ospemifene is a selective estrogen receptor modulator (SERM) that selectively binds to estrogen receptors and either stimulates or blocks estrogen's activity in different tissue types. It has an agonistic effect on the endometrium. It’s building vaginal wall thickness which in turn reduces the pain associated with dyspareunia. Dyspareunia is most commonly caused by "vulval and vaginal atrophy”.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor 75 Target ID: P03372 Gene ID: 2099.0 Gene Symbol: ESR1 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/23945733	Modulator 828		827.0 nM [IC50]
Estrogen receptor beta 110 Target ID: Q92731\|\|\|O75584 Gene ID: 2100.0 Gene Symbol: ESR2 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/23945733	Modulator 828		1633.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dyspareunia 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203505s005lbl.pdf	Curative		Approved 8429	OSPHENA Approved Use Indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause Launch Date 2013

C_max

Value	Dose	Co-administered	Analyte	Population
533 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OSPEMIFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
4165 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OSPEMIFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
26 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		OSPEMIFENE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

Doses

Dose	Population	Adverse events
200 mg 1 times / day steady, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12443837	healthy, 62 years (range: 55 - 75 years) n = 8 Health Status: healthy Age Group: 62 years (range: 55 - 75 years) Sex: F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/12443837	Disc. AE: Hot flushes, Dizziness... AEs leading to discontinuation/dose reduction: Hot flushes (1 patient) Dizziness (1 patient) Chest pain Sources: https://pubmed.ncbi.nlm.nih.gov/12443837
60 mg 1 times / day multiple, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf	unhealthy, adult (Postmenopausal) Health Status: unhealthy Age Group: adult (Postmenopausal) Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf	Other AEs: Thromboembolic stroke, Hemorrhagic stroke... Other AEs: Thromboembolic stroke Hemorrhagic stroke Deep vein thrombosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf
60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114	unhealthy, adult (Postmenopausal) n = 301 Health Status: unhealthy Condition: Vulvar and Vaginal Atrophy Age Group: adult (Postmenopausal) Sex: F Population Size: 301 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114	Disc. AE: Nausea, Muscle spasms... AEs leading to discontinuation/dose reduction: Nausea (1%) Muscle spasms (0.7%) Headache (1%) Hyperhidrosis (0.7%) Rash (0.7%) Hot flush (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114

AEs

AE	Significance	Dose	Population
Dizziness	1 patient Disc. AE	200 mg 1 times / day steady, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12443837	healthy, 62 years (range: 55 - 75 years) n = 8 Health Status: healthy Age Group: 62 years (range: 55 - 75 years) Sex: F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/12443837
Hot flushes	1 patient Disc. AE	200 mg 1 times / day steady, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12443837	healthy, 62 years (range: 55 - 75 years) n = 8 Health Status: healthy Age Group: 62 years (range: 55 - 75 years) Sex: F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/12443837
Chest pain	Disc. AE	200 mg 1 times / day steady, oral Highest studied dose Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12443837	healthy, 62 years (range: 55 - 75 years) n = 8 Health Status: healthy Age Group: 62 years (range: 55 - 75 years) Sex: F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/12443837
Deep vein thrombosis		60 mg 1 times / day multiple, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf	unhealthy, adult (Postmenopausal) Health Status: unhealthy Age Group: adult (Postmenopausal) Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf
Hemorrhagic stroke		60 mg 1 times / day multiple, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf	unhealthy, adult (Postmenopausal) Health Status: unhealthy Age Group: adult (Postmenopausal) Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf
Thromboembolic stroke		60 mg 1 times / day multiple, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf	unhealthy, adult (Postmenopausal) Health Status: unhealthy Age Group: adult (Postmenopausal) Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203505s000lbl.pdf
Hyperhidrosis	0.7% Disc. AE	60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114	unhealthy, adult (Postmenopausal) n = 301 Health Status: unhealthy Condition: Vulvar and Vaginal Atrophy Age Group: adult (Postmenopausal) Sex: F Population Size: 301 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114
Muscle spasms	0.7% Disc. AE	60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114	unhealthy, adult (Postmenopausal) n = 301 Health Status: unhealthy Condition: Vulvar and Vaginal Atrophy Age Group: adult (Postmenopausal) Sex: F Population Size: 301 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114
Rash	0.7% Disc. AE	60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114	unhealthy, adult (Postmenopausal) n = 301 Health Status: unhealthy Condition: Vulvar and Vaginal Atrophy Age Group: adult (Postmenopausal) Sex: F Population Size: 301 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114
Headache	1% Disc. AE	60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114	unhealthy, adult (Postmenopausal) n = 301 Health Status: unhealthy Condition: Vulvar and Vaginal Atrophy Age Group: adult (Postmenopausal) Sex: F Population Size: 301 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114
Nausea	1% Disc. AE	60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114	unhealthy, adult (Postmenopausal) n = 301 Health Status: unhealthy Condition: Vulvar and Vaginal Atrophy Age Group: adult (Postmenopausal) Sex: F Population Size: 301 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114
Hot flush	2% Disc. AE	60 mg 1 times / day steady, oral Recommended Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114	unhealthy, adult (Postmenopausal) n = 301 Health Status: unhealthy Condition: Vulvar and Vaginal Atrophy Age Group: adult (Postmenopausal) Sex: F Population Size: 301 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000MedR.pdf Page: p. 114

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037 inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 810 CYP2C19 1478 CYP2C8 911	CYP2C19 991 P-gp 1537	CYP 76

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000PharmR.pdf Page: 11.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 5, 66	yes [IC50 10 uM]	yes (co-administration study) Comment: ospemifene inhibited CYP2B6, CYP2C9, CYP2C19, CYP2C8 and CYP2D6 with IC50 values in the range of 7.8-49 μM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 5, 66
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 5, 66	yes [IC50 35 uM]	yes (co-administration study) Comment: ospemifene inhibited CYP2B6, CYP2C9, CYP2C19, CYP2C8 and CYP2D6 with IC50 values in the range of 7.8-49 μM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 5, 66
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 5, 66	yes [IC50 7.8 uM]	yes (co-administration study) Comment: ospemifene inhibited CYP2B6, CYP2C9, CYP2C19, CYP2C8 and CYP2D6 with IC50 values in the range of 7.8-49 μM Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 5, 66
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 66.0	yes
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 66.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 9, 32, 40, 66	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 9, 11, 18	yes	yes (co-administration study) Comment: omeprazole increased Cmax 1.2-fold and AUC 1.17-fold, fluconazole increased Cmax 1.7-fold and AUC 2.7-fold; rifampin reduced Cmax by 51% and AUC by 58% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 9, 11, 18
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 9, 11, 18	yes	yes (co-administration study) Comment: fluconazole increased Cmax 1.7-fold and AUC 2.7-fold; rifampin reduced Cmax by 51% and AUC by 58% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 9, 11, 18
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 9, 10, 11, 18	yes	yes (co-administration study) Comment: ketoconazole increased Cmax 1.5-fold and AUC by 1.4-fold, fluconazole increased Cmax 1.7-fold and AUC 2.7-fold; rifampin reduced Cmax by 51% and AUC by 58% Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000ClinPharmR.pdf Page: 9, 10, 11, 18

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203505Orig1s000PharmR.pdf Page: 24.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:73275	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:73275
ChemicalBook	CB01335273	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB01335273
MolPort	MolPort-006-170-032	https://www.molport.com/shop/molecule-link/MolPort-006-170-032
ZINC	ZINC000001550766	http://zinc15.docking.org/substances/ZINC000001550766

PubMed

Title	Date	PubMed
Effects of ospemifene, a novel SERM, on vascular markers and function in healthy, postmenopausal women.	2003 Sep-Oct	14501606

Patents

Sample Use Guides

In Vivo Use Guide

One tablet (60 mg ) taken orally once daily with food

Route of Administration: Oral

In Vitro Use Guide

The growth inhibitory effects of FC-1271a and its main metabolite are investigated in MCF-7 and MDA-MB-231 human breast cancer cells at doses ranging from 0.1 to 10 uM.

Name

Type

Language

OSPEMIFENE

Official Name

English

(DEAMINOHYDROXY) TOREMIFENE

Common Name

English

SENSHIO

Brand Name

English

TORE III

Common Name

English

OSPEMIFENE [MART.]

Common Name

English

OSPEMIFENE [ORANGE BOOK]

Common Name

English

ospemifene [INN]

Common Name

English

FC-1271

Code

English

Ospemifene [WHO-DD]

Common Name

English

OSPEMIFENE [MI]

Common Name

English

ETHANOL, 2-(4-((1Z)-4-CHLORO-1,2-DIPHENYL-1-BUTENYL)PHENOXY)-

Systematic Name

English

OSPEMIFENE [USAN]

Common Name

English

OSPHENA

Brand Name

English

OSPEMIFENE [VANDF]

Common Name

English

FC-1271A

Code

English

2-(P-((Z)-4-CHLORO-1,2-DIPHENYL-1-BUTENYL)PHENOXY)ETHANOL

Common Name

English

Classification Tree Code System Code

WHO-VATC

QG03XC05